LSD: History, Science, and Modern Research

Basel, 1938 and 1943

Lysergic acid diethylamide was made by Albert Hofmann, a chemist in Arthur Stoll's pharmaceutical laboratory at Sandoz in Basel. Working through derivatives of lysergic acid, a component of the ergot fungus, he produced the twenty-fifth in the series in 1938 and called it LSD-25 for laboratory use. He had hoped for a circulatory and respiratory stimulant; animal tests aroused no special interest and testing was discontinued for five years. (Multidisciplinary Association for Psychedelic Studies (online edition), 1980)

In the spring of 1943 Hofmann made it again. On Friday 16 April he had to leave the laboratory with restlessness, dizziness and a stream of vivid images that faded after about two hours; he suspected a trace had been absorbed through his fingertips. On 19 April he deliberately took 0.25 mg, which he chose as the smallest amount likely to have any effect. It was in fact a large dose, and he went home by bicycle in the most severe part of the experience. (Multidisciplinary Association for Psychedelic Studies (online edition), 1980) Many retellings merge the two days: the accidental exposure was on the 16th, the bicycle ride on the 19th.

This page covers LSD's history and science. For the current evidence on LSD for drinking problems, the psychedelics for alcohol use disorder page is the place to look, and the LSD substance page has the basic profile.

Delysid and the research decades

The first systematic study in people was led by Werner Stoll, Arthur Stoll's son, at the University of Zurich psychiatric clinic and published in 1947. Sandoz then supplied LSD to researchers and physicians as an experimental drug under the trade name Delysid. Its prospectus suggested two uses: as an aid in analytical psychotherapy, and for psychiatrists to take themselves to gain insight into psychosis. It warned that LSD could intensify existing mental illness and should be given only under strict medical supervision. (Multidisciplinary Association for Psychedelic Studies (online edition), 1980)

Sandoz made LSD available free of charge to qualified investigators for close to two decades. In a letter of 23 August 1965 it announced it would stop all production and distribution of LSD and psilocybin, citing sensational publicity, unregulated supply and growing misuse. Supply later resumed only to researchers with national permits; in the United States, the National Institute of Mental Health took over distribution. (Multidisciplinary Association for Psychedelic Studies (online edition), 1980)

The alcoholism trials

Some of the most studied uses in that period were for alcoholism. In 2012 Teri Krebs and Pål-Ørjan Johansen pooled six randomised controlled trials with 536 participants. A single LSD dose was associated with less alcohol misuse at follow-up (odds ratio 1.96), with negligible variation between trials. (Journal of Psychopharmacology, 2012) The trials were decades old and used methods that would not meet today's standards, so the result is a signal rather than proof. A Basel trial of LSD for alcohol use disorder is now recruiting. (ClinicalTrials.gov, 2026) Recruiting studies are on the alcohol use disorder trials page.

MKUltra: the CIA's LSD experiments

Alongside medical research ran a covert one. At a 1977 Senate hearing, the Director of Central Intelligence, Admiral Stansfield Turner, described MKULTRA as a closely held CIA "umbrella project" run from 1953 to 1964 that funded research on drugs and behaviour modification. He reported 149 subprojects, including some involving tests on unwitting subjects. (US Government Printing Office (copy hosted by the Central Intelligence Agency), 3 Aug 1977)

Senator Edward Kennedy told the same hearing that the testing had involved over 30 universities and institutions, that several tests gave LSD to "unwitting subjects in social situations", and that newly found records raised the count to 86 universities or institutions. Records of the programme had been destroyed in January 1973 on the instruction of then CIA Director Richard Helms. (US Government Printing Office (copy hosted by the Central Intelligence Agency), 3 Aug 1977) Turner described the death of Frank Olson, an Army civilian employee at Fort Detrick, who fell from a New York hotel window in 1953 about a week after unwittingly being given LSD at a CIA-called meeting. (US Government Printing Office (copy hosted by the Central Intelligence Agency), 3 Aug 1977)

Prohibition: 1968, 1970, 1971

• 1968. Public Law 90-639, signed on 24 October 1968, named LSD in the federal drug law and made possessing it without a prescription an offence, punishable on a first conviction by up to a year in prison or a $1,000 fine. (US Government Publishing Office (govinfo), 24 Oct 1968)
• 1970. The Controlled Substances Act, enacted on 27 October 1970, lists lysergic acid diethylamide in Schedule I, the category for drugs with a high potential for abuse and no currently accepted medical use in the United States. (Legal Information Institute (Cornell), current) It remains there today, as do DMT, psilocybin and mescaline. (Legal Information Institute (Cornell) reproducing the U.S. Code, current)
• 1971. The UN Convention on Psychotropic Substances, adopted in Vienna on 21 February 1971, lists lysergide (LSD) in Schedule I, its most restrictive category. (United Nations Office on Drugs and Crime, 1971)

Research did not stop entirely, but human studies with LSD became rare. A 2015 Basel paper described renewed interest in LSD after no research in humans for more than 40 years. (Biological Psychiatry, 2015)

Pharmacology

LSD acts mainly as an agonist or partial agonist at serotonin 5-HT2A receptors, the consensus target for classic psychedelics. (Pharmacological Reviews, 2016) It is extremely potent: in a controlled study of healthy volunteers, doses of 6.5, 13 and 26 micrograms produced dose-related subjective effects. (Biological Psychiatry, 2019)

Its long action has a structural explanation. A 2017 crystal structure of LSD bound to the closely related 5-HT2B receptor showed LSD leaving both 5-HT2B and 5-HT2A exceptionally slowly. Simulations suggested a "lid" formed by a loop of the receptor closes over the binding pocket, and a mutation that loosened the lid sped up LSD's binding. (Cell, 2017)

In pooled Basel studies, plasma half-life was 2.6 hours, but subjective effects lasted on average 8.2 hours after 100 micrograms and 11.6 hours after 200 micrograms. (Clinical Pharmacokinetics, 2017) At 200 micrograms LSD raised blood pressure, heart rate, body temperature and pupil size, and adverse effects had cleared within 72 hours. (Biological Psychiatry, 2015)

What it does in the brain

The first modern imaging study, at Imperial College London, combined three techniques. Visual hallucinations tracked increased blood flow and expanded connectivity in the visual cortex, while ego dissolution tracked reduced connectivity between the parahippocampus and retrosplenial cortex. (Proceedings of the National Academy of Sciences, 2016) A companion analysis found LSD increased global connectivity in areas rich in 5-HT2A receptors, and that this rise correlated with ego dissolution. (Current Biology, 2016)

The modern trials

Anxiety with life-threatening illness

In a Swiss pilot led by Peter Gasser, 12 patients with anxiety linked to a life-threatening illness had two LSD-assisted psychotherapy sessions at 200 micrograms or an active placebo of 20 micrograms. State anxiety fell significantly at 2 months, reductions held at 12 months, and no adverse effects lasted beyond a day. (Journal of Nervous and Mental Disease, 2014) Follow-up interviews found no lasting adverse reactions. (Journal of Psychopharmacology, 2015)

Anxiety with or without serious illness

Friederike Holze and colleagues ran a double-blind, placebo-controlled crossover trial in 42 patients. Two 200 microgram sessions reduced anxiety scores significantly up to 16 weeks later (effect size d -1.18). Eight patients (19%) had transient, mild acute effects and one had a serious adverse event, acute transient anxiety. (Biological Psychiatry, 2023) A year later, 39 participants still reported lower anxiety than at baseline. (British Journal of Psychiatry, 2024)

MM120 for generalised anxiety disorder

The company MindMed, renamed Definium Therapeutics in January 2026, developed MM120, an LSD tablet now called DT120. (US Securities and Exchange Commission (EDGAR), 2026; Expert Review of Neurotherapeutics, 2026) In its phase 2b trial, 198 adults with moderate to severe generalised anxiety disorder at 22 US sites received one dose of 25, 50, 100 or 200 micrograms or placebo, without protocol-mandated psychotherapy. At 4 weeks the 100 and 200 microgram doses reduced anxiety (HAM-A) by 5.0 and 6.0 points more than placebo; the lower doses did not differ significantly. Visual perceptual changes occurred in 92.5% and 100% of those groups, and nausea and headache were common. (JAMA, 2025)

The company then announced positive topline results from two phase 3 trials of a single 100 microgram dose. In Voyage (214 participants), anxiety fell 5.4 points more than with placebo at week 12. (US Securities and Exchange Commission (EDGAR), 12 Aug 2026) In Panorama, announced on 14 September 2026, the difference was 5.1 points. (US Securities and Exchange Commission (EDGAR), 14 Sep 2026) These are company press releases filed with the SEC; full peer-reviewed reports had not appeared by mid-September 2026. (Expert Review of Neurotherapeutics, 2026) As of October 2026 DT120 remains an investigational drug. (Expert Review of Neurotherapeutics, 2026) The anxiety trials page and the end-of-life distress trials page, where a Basel palliative care study is listed, show what is recruiting. (ClinicalTrials.gov, 2024)

Safety

Controlled trials report side effects that are mostly short-lived, but they screen participants carefully. Research guidelines exclude people with a personal or family history of psychotic disorders. (Journal of Psychopharmacology, 2008; Oregon Health Authority, Public Health Division, 2026) Lithium is a particular concern: in an analysis of online reports of lithium taken with a classic psychedelic such as LSD, 47% of 62 involved seizures. (Pharmacopsychiatry, 2021; Oregon Health Authority, Public Health Division, 2026) A small study of people taking tricyclic antidepressants found stronger LSD responses. (Behavioural Brain Research, 1996) The interaction checker covers more combinations; anyone on a prescribed medicine should talk to their prescriber rather than change it themselves.

In a US population survey of more than 130,000 adults, lifetime LSD use was not associated with higher rates of the mental health problems studied. (PLoS ONE, 2013) That does not rule out harm to individuals, especially without supervision. LSD remains Schedule I in the US, and the Legal page covers other countries.